11/04/2023 1

Bleeding and coagulation disorders in

childrenDr.K.V.Giridhar

Associate Prof. of Pediatrics

GMC. Ananthapuramu, A.P.,India.

Definition:• Spontaneous bleeding.• Excessive & Prollanged bleeding following trauma.

• Petechiae, purpura, echymosis, bruises, hematoma, hemarthrosis, IC bleeds, occult GI bleeds, melena, epistaxis.

Bleeding disorders

Coagulation

disorders

Hemostasis

Tissue phasePlatelet phaseClotting PhaseUnstable clot PhaseClot stabilization PhaseClot retraction PhaseClot resolving Phase

THE CLOTTING MECHANISM

INTRINSIC EXTRINSIC

PROTHROMBIN(II) THROMBIN(III)

FIBRINOGEN

FIBRIN

(I)V

X

Tissue ThromboplastinCollagen

VIIXII

XI

IXVIII

VII

PTPTT Vit.K, Liver

Etiology

• VESSEL WALL ABNORMALITIES:

• PLATELETS DISORDER:

• COAGULATION DISORDER:

Vessel Abnormalities• increased vascular fragility• manifest by petechial hemorrhages of

skin/mucous membranes• not life threatening bleeding1. congenital: a. Ehlers-Danlos syndrome (AD)

b. hereditary hemorrhagic telangiectasia (AD)

2. acquired: a. hypersensitive vasculitis(i) drug reaction : immune complex

deposit in vessel walls(Thaizide diuetics)(ii) Henoch-Schonlein purpura

b. scurvy (vit C deficiency)

Lab: BT, Plt count, PT, PTT will be normal

VESSEL WALL ABNORMALITIES:

EHLERS DANLOS DISEASE:• Congenital disorder of collagen

synthesis • in which capillaries are poorly

supported by s/c collagen• ecchymosis are commonly

observed.

VESSEL WALL ABNORMALITIES:HERIDITARY HEMORHAGIC TELANGECTSIASIS• Dominant inherited condition.• Telengectias, are small aneurysms found on

finger tips, face, nasal passages, tongue and GIT.

• few people develop pulmonary A/V malformation.

• Pt. develops recurrent bleeding/epistaxis/ occult GIT bleeding, leads to Iron def. anemia

Rx.• Iron therapy for blood loss.• Local cautery/laser therapy for single lesion• Estrogens may be tried.

Henoch-Schonlein purpura(nonthrombocytopenic)

• generalized hypersensitivity vasculitis

• uncertain cause(immune mediated)clinical Sx:

• Purpura(palpable)• colicky abdominal pain• polyarthralgia• acute glomerulonephritis

Rx: Prednisolone for2-4 weeks

PLATELETS DISORDER:

• QUANTITATIVE PLATELETS DISORDERs

• QUALITATIVE PLATELET DYSFUNCTION :

QUANTITATIVE PLATELETS DISORDER (Thrombocytopenia)

Mechanisms:1 Failure of megakaryocytic maturation.2 Excessive platelets consumption after their

release into circulation i.e ITP, DIC etc.3 Platelets sequestration in enlarged spleen i.e

HYPERSPLEENISM. S/S:·  Petechial cutaneous bleeding, intracranial

bleeding and oozing from mucus membrane & skin surface.

·  Lab: decreased platelets count and prolong bleeding time.

(Thrombocytopenia) Causes:

Marrow DisorderAplastic anemiaHem. malignancyMyelodysplastic

disorderB12 deff.

Non Marrow DisorderImmune disordersITP, Drug inducedSec: ALL, SLEPost transfusionDIC, TTPHU syndrome, HyperspleenismHeamangiomasSepsisViral infection

Management:

Rx Underlying cause

Platelet transfusion

IDIOPATHIC THROMBOCYTOPENIC PURPURA(ITP)

• An autoimmune antibody IgG is formed against unknown antigen of platelets membrane/surface.

• Antipletelet antibody binds to complement, but platelets are not destroyed by direct lysis.

• Destruction takes place in spleen, where spleenic macrophages destroyes antibody coated platelets.

IDIOPATHIC THROMBOCYTOPENIC PURPURA. (Clinical Features)

In Children(acute):Often precipitated by viral infection and

usually self limited Asymptomatic not febrile. Present with mucosal/skin bleeding,

mennorrhagia, purpura, petechiae.Adults(chronic): Commonly affects female. Ratio 2:1 (male/female ratio) Peak incidence 20-50 years of age.

IDIOPATHIC THROMBOCYTOPENIC

PURPURA. Δ LAB:platelets below 10,000 /ml.Bone marrow will appear normal.RxPREDNISONONE: 1-2 mg/kg/day. Immunoglobulin: 1g/kg/day 2-3 days.DANAZOLE: 600mg/day response rate is 50%IMMUNOSUPPERESSIVE DRUGS: i-e vincristine,

vinblastine, azathioprine, cyclosprin, cyclophosphomide.

SPLEENECTOMY:Prognosis:The prognosis will be good, if disease is initially

controlled with prednisolone, spleenectomy is definite Rx.

EVANS SYNDROME:

• ITP + Autoimmune hemolytic anemia.

• These pts shows spherocytosis, reticulocytosis + anemia.

QUALITATIVE PLATELET DISORDER

CONGENITAL:Glanzmann’s

thrombosthenia

Bernard souliar syndrome

Von Willibrand’s disease

ACQUIRED

Myeloproliferative disorder.

Uremia

Drugs i-e NSAIDS Aspirin

Autoantibody

Fibrin degradation products

QUALITATIVE PLATELET DISORDERBERNARD SOULIER SYNDROME:Autosomal recessive intrinsic platelets disorder.Due to lack of glycoprotein (Gp1b), receptor for

vonWillibrand’s factor.Clinical Features:Presents with mucosal bleeding and post

operative oozes.LAB:Thrombocytopenia may be present, and Plt.s are

abnormally large in size.BT is prolonged Von Willibrand’s factor Normal Rx:Platelet transfusion

QUALITATIVE PLATELET DISORDERGLANZMANN’s THROMBASTHENIA:

Autosomal recessive disorder.Lack of receptors (glycoprotein Ib & IIIa)

for fibrinogen on platelets.Platelets fails to aggregate in respons to

ADP, collagen, thrombin.Clinical Features: Mucosal bleedingLAB:Platelets no’s and morphology are normal B.T is prolonged Rx:Platelet transfusion

QUALITATIVE PLATELET DISORDERVON-WILLIBRAND’S DISEASE:• Autosomal dominant(gene for vWF is

located on chromosome 12.)• vWF is synthesized by endothelial

cells and megakaryocytes • It acts as carrier protein for factor

VIII by non-covalent bond. A defect therefore leads to decreased plasma factor VIII level.

• It also forms bridges b/w platelets and sub endothelium.

• There fore defect of vWF leads to prolonged bleeding.

VON-WILLIBRAND’S DISEASE:Clinical Features:• Mucosal bleeding (mild-massive)LAB:• Reduced level of vWF which often

accomplished by sec: reduction in factor VIII and prolonged bleeding time (B.T)

Rx:• MILD HAEMORRHAGES:Desmopressin 0.3 μg/kg, after which vWF

levels usually raise 3 in 30-90 minutes • MASSIVE HAEMORRHAGES:Factor VIII

COAGULATION DISORDER:

Coagulation factor disorder can either due to single factor def., i.e. a “congenitaldeficiency”, eg factor VIII resulting in HAEMOPHILIA-A

or due to multiple factor def., which is an ‘’acquired” eg Sec: to liver disease or warfarin therapy.

• HEAMOPHILIA – A (CLASSIC TRUE HAEMOPHILIA)

• HAEMOPHILLIA – B (CHRISTMAS DISEASE).

• X-linked recessive Inheritance.

COAGULATION DISORDER:CONGENITAL BLEEDING DISORDER:

HEAMOPHILIA – A (CLASSIC TRUE HAEMOPHILIA)• X-linked disorder • Due to deff. of factor VIIIC/F:• Bleeding occurs as bruising at the age of 6

months.• Trauma results in excessively bleeding.• Recurrent bleeding /hemorrhage in knee,

elbow, ankle, and hip. (Hemarthrosis)• Mucus membrane /internal bleeding of

mouth, lips, gums, brain and kidney also occur• Muscle haematoma esp. calf and Psoas muscle Rx• Factor VIII infusion

Hemophilia A

HAEMOPHILLIA – B (CHRISTMAS DISEASE)

• Due to deff: of factor IX S/S:• Same in type ARx• Factor IX infusionLONG TERM COMPLICATIONCOMPLICATION due to repeated hemorrhage:• Arthropathy of large joints eg knee, elbow• Muscle atrophy due to haematoma• Mononeuropathy due to pressure of haematoma.COMPLICATION due to therapy• Antifactor VIII antibody develops• Virus transmission Hepatitis A-B-C-D + HIV

COAGULATION DISORDERACQUIRED BLEEDING DISORDER

• DIC• LIVER DISEASE • RENAL DISEASE

DISSAMINATED INTRAVASCULAR COAGULATION

• DIC is condition characterized by thrombosis within circulation.

• DIC can be induced by different mechanisms.• Due to Endothelial cell damage by endotoxins in

G –ve septicemia results in tissue factor release which in turn leads to coagulation cascade activation through extrinsic pathway.

• The presence thromboplastin from damaged tissue, placenta & fat embolus (following brain injury & Fractures) may activate coagulation

• This results in excessive consumption of platelets and coagulation factors, with secondary activation of fibrinolysis leading to bleeding tendency.

DIC:

CAUSESInfectious:• E Coli• Nessieria

meningitis• Strep pneumonia• MalariaCancer • Lung,Pancreas,• Prostate

CLINICAL FEATURES:

Bleeding & thrombosis, bleeding is more than thrombosis.

Subacute DIC:

Occurs primarily in cancerous pts results in superficial + deep venous thrombosis.

Other Manifestation:

High incidence of cardio respiratory failure

DIC

LAB:• Thrombocytopenia• Prolong PT• APTT may be normal/increased• Low fibrinogen• Increased level FDP/D-dimmer

Treatment of DIC

Rx. Underlying cause.General Measures:• Correction of dehydration• Renal failure• Acidosis and • ShockReplacement:• Platelets transfusion if platelets counts below

10,000/l• cryoprecipitate to maintain plasma fibrinogen

level above 150 mg/dl • FFP• Heparin, if there is DVT, Pulmonarythrombosis.

Approach to a child with bleeding disorder

Bleeding Not sick sic

kSuperficial bleeds

Deep Bleeds

CBC, BT Factor assay, Gene analysis

Bone marrow

Blood culture

CBC, Bonemarrow

LFT

RFT

FDP

THANKYOU